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邻苯二甲酸二(2-乙基己基)酯和邻苯二甲酸二乙酯会破坏脂质代谢,降低秀丽隐杆线虫的繁殖力并缩短其寿命。

Di(2-ethylhexyl) phthalate and diethyl phthalate disrupt lipid metabolism, reduce fecundity and shortens lifespan of Caenorhabditis elegans.

机构信息

Biology, the Life Science Center, School of Science and Technology, Örebro University, SE-701 82 Örebro, Sweden.

Biology, the Life Science Center, School of Science and Technology, Örebro University, SE-701 82 Örebro, Sweden.

出版信息

Chemosphere. 2018 Jan;190:375-382. doi: 10.1016/j.chemosphere.2017.09.123. Epub 2017 Sep 28.

DOI:10.1016/j.chemosphere.2017.09.123
PMID:29020644
Abstract

The widespread use of phthalates is of major concern as they have adverse effects on many different physiological functions, including reproduction, metabolism and cell differentiation. The aim of this study was to compare the toxicity of the widely-used di (2-ethydlhexyl) phthalate (DEHP) with its substitute, diethyl phthalate (DEP). We analyzed the toxicity of these two phthalates using Caenorhabditis elegans as a model system. Gene expression analysis following exposure during the L1 to young adult stage showed that DEHP and DEP alter the expression of genes involved in lipid metabolism and stress response. Genes associated with lipid metabolism, including fasn-1, pod-2, fat-5, acs-6 and sbp-1, and vitellogenin were upregulated. Among the stress response genes, ced-1 wah-1, daf-21 and gst-4 were upregulated, while ctl-1, cdf-2 and the heat shock proteins (hsp-16.1, hsp-16.48 and sip-1) were downregulated. Lipid staining revealed that DEHP significantly increased lipid content following 1 μM exposure, however, DEP required 10 μM exposure to elicit an effect. Both DEHP and DEP reduced the fecundity at 1 μM concentration. Lifespan analysis indicated that DEHP and DEP reduced the average lifespan from 14 days in unexposed worms to 13 and 12 days, respectively. Expression of lifespan associated genes showed a correlation to shortened lifespan in the exposed groups. As reported previously, our data also indicates that the banned DEHP is toxic to C. elegans, however its substitute DEP has not been previously tested in this model organism and our data revealed that DEP is equally potent as DEHP in regulating C. elegans physiological functions.

摘要

邻苯二甲酸酯的广泛使用引起了人们的极大关注,因为它们对许多不同的生理功能都有不良影响,包括生殖、代谢和细胞分化。本研究旨在比较广泛使用的邻苯二甲酸二(2-乙基己基)酯(DEHP)与其替代品邻苯二甲酸二乙酯(DEP)的毒性。我们使用秀丽隐杆线虫作为模型系统来分析这两种邻苯二甲酸酯的毒性。暴露于 L1 至幼年期后的基因表达分析表明,DEHP 和 DEP 改变了与脂质代谢和应激反应相关的基因表达。与脂质代谢相关的基因,包括 fasn-1、pod-2、fat-5、acs-6 和 sbp-1 以及卵黄蛋白原,被上调。在应激反应基因中,ced-1、wah-1、daf-21 和 gst-4 被上调,而 ctl-1、cdf-2 和热休克蛋白(hsp-16.1、hsp-16.48 和 sip-1)被下调。脂质染色显示,DEHP 在暴露于 1μM 时显著增加了脂质含量,而 DEP 需要 10μM 暴露才能产生效果。DEHP 和 DEP 都在 1μM 浓度下降低了生殖力。寿命分析表明,DEHP 和 DEP 将未暴露线虫的平均寿命从 14 天分别缩短至 13 天和 12 天。暴露组中与寿命相关的基因表达与寿命缩短相关。正如先前报道的那样,我们的数据还表明,被禁用的 DEHP 对 C.elegans 有毒性,但 DEP 以前在这种模式生物中没有被测试过,我们的数据显示,DEP 在调节 C.elegans 生理功能方面与 DEHP 同样有效。

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